Dimeric Antigen Receptors for CD20 Targeting

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current chimeric antigen receptors (CARs) used in cancer treatment, such as those targeting CD19, have limitations in efficacy and persistence within patients, leading to suboptimal tumor eradication and potential relapse due to insufficient activation and memory T cell formation.

Innovation Solution

Development of dimeric antigen receptors (DARs) comprising two polypeptides that form a Fab fragment, with one chain including a transmembrane and intracellular signaling domain, specifically targeting CD20, to enhance tumor cell recognition and persistence by forming memory T cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If first-generation CAR with single signaling domain is used, then device complexity is reduced, but anti-tumor efficacy is insufficient

Engineering Contradiction:

ImproveCAR structure complexityVSAvoidanti-tumor efficacy

Core Design Contradiction:

Device complexityVSReliability

Solution Approach 1:

The patent combines multiple signaling domains (TCRζ and CD28) into a single chimeric signaling domain, creating a dual-function signaling unit that provides both activation signal and costimulation. This merging approach increases anti-tumor efficacy without proportionally increasing structural complexity, as the two signaling functions are integrated into one domain rather than requiring separate structural components.

Inventive Principle:

Principle #5Merging (Combining)

2Reliability

If CAR-T cells are used for tumor treatment, then tumor cell recognition is improved, but persistence and memory T cell formation are insufficient

Engineering Contradiction:

Improvetumor cell recognitionVSAvoidT cell persistence

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent modifies the signaling parameters of the CAR by incorporating specific costimulatory domains (CD28, 4-1BB, or OX40) that alter the activation threshold and signaling intensity. This parameter change enables the T cells to maintain persistent activation and form memory phenotypes, thereby extending the duration of action and persistence without compromising tumor recognition capability.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If second-generation CAR with costimulatory domain is used, then anti-tumor capacity is increased, but device complexity increases

Engineering Contradiction:

Improveanti-tumor capacityVSAvoidCAR structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges the costimulatory domain with the signaling domain to create an integrated chimeric signaling domain. This merging strategy allows the CAR to incorporate multiple functional elements (activation signaling and costimulation) while maintaining a relatively compact structure, thus increasing anti-tumor capacity without proportionally increasing overall device complexity.

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS20230061838A1Dimeric Antigen Receptors (DAR) That Bind CD20

Publication Date: 2023.03.02 VIVASOR INC

AI summary

The present disclosure provides dimeric antigen receptors (DAR) constructs that bind a CD20 target antigen, where the DAR construct comprises a heavy chain binding region on one polypeptide chain and a light chain binding region on a separate polypeptide chain. The two polypeptide chains that make up the dimeric antigen receptors can dimerize to form an antigen binding domain. The dimeric antigen receptors have antibody-like properties as they bind specifically to a target antigen. The dimeric antigen receptors can be used for directed cell therapy.